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基于自噬相关基因的 LUAD 患者个体化临床预后标志物的建立和验证。

Establishment and validation of individualized clinical prognostic markers for LUAD patients based on autophagy-related genes.

机构信息

Department of Integrated Chinese and Western Medicine, The First People's Hospital of Jiashan, Jiaxing, Zhejiang, China.

Information Center, The First People's Hospital of Jiashan, Jiaxing, Zhejiang, China.

出版信息

Aging (Albany NY). 2022 Sep 29;14(18):7328-7347. doi: 10.18632/aging.204097.

Abstract

There is considerable heterogeneity in the genomic drivers of lung adenocarcinoma, which has a dismal prognosis. Bioinformatics analysis was performed on lung adenocarcinoma (LUAD) datasets to establish a multi-autophagy gene model to predict patient prognosis. LUAD data were downloaded from The Cancer Genome Atlas (TCGA) database as a training set to construct a LUAD prognostic model. According to the risk score, a Kaplan-Meier cumulative curve was plotted to evaluate the prognostic value. Furthermore, a nomogram was established to predict the three-year and five-year survival of patients with LUAD based on their prognostic characteristics. Two genes (ITGB1 and EIF2AK3) were identified in the autophagy-related prognostic model, and the multivariate Cox proportional risk model showed that risk score was an independent predictor of prognosis in LUAD patients (HR=3.3, 95%CI= 2.3 to 4.6, < 0.0001). The Kaplan-Meier cumulative curve showed that low-risk patients had significantly better overall (<0.0001). The validation dataset GSE68465 further confirmed the nomogram's robust ability to assess the prognosis of LUAD patients. A prognosis model of autophagy-related genes based on a LUAD dataset was constructed and exhibited diagnostic value in the prognosis of LUAD patients. Moreover, real-time qPCR confirmed the expression patterns of EIF2AK3 and ITGB1 in LUAD cell lines. Two key autophagy-related genes have been suggested as prognostic markers for lung adenocarcinoma.

摘要

肺腺癌的基因组驱动因素存在相当大的异质性,预后较差。对肺腺癌(LUAD)数据集进行了生物信息学分析,建立了一个多自噬基因模型,以预测患者的预后。从癌症基因组图谱(TCGA)数据库下载 LUAD 数据作为训练集,构建 LUAD 预后模型。根据风险评分,绘制 Kaplan-Meier 累积曲线以评估预后价值。此外,根据预后特征建立列线图预测 LUAD 患者的三年和五年生存率。在自噬相关预后模型中鉴定出两个基因(ITGB1 和 EIF2AK3),多变量 Cox 比例风险模型显示风险评分是 LUAD 患者预后的独立预测因子(HR=3.3,95%CI=2.3 至 4.6,<0.0001)。Kaplan-Meier 累积曲线显示低风险患者的总体生存率显著提高(<0.0001)。验证数据集 GSE68465 进一步证实了列线图评估 LUAD 患者预后的稳健能力。构建了基于 LUAD 数据集的自噬相关基因预后模型,该模型在 LUAD 患者的预后诊断中具有价值。此外,实时 qPCR 证实了 EIF2AK3 和 ITGB1 在 LUAD 细胞系中的表达模式。这两个关键的自噬相关基因已被认为是肺腺癌的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3825/9550247/900a60a64ffc/aging-14-204097-g001.jpg

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